Wang Jingchen, Tao Jianmei, Jia Shuailong, Wang Meiqin, Jiang Hongliang, Du Zhifeng
School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Pharmaceuticals (Basel). 2021 Jan 29;14(2):104. doi: 10.3390/ph14020104.
Cisplatin and its analogues are widely used as chemotherapeutic agents in clinical practice. After being intravenously administrated, a substantial amount of platinum will bind with proteins in the blood. This binding is vital for the transport, distribution, and metabolism of drugs; however, toxicity can also occur from the irreversible binding between biologically active proteins and platinum drugs. Therefore, it is very important to study the protein-binding behavior of platinum drugs in blood. This review summarizes mass spectrometry-based strategies to identify and quantitate the proteins binding with platinum anticancer drugs in blood, such as offline high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) combined with electrospray ionization mass spectrometry (ESI-MS/MS) and multidimensional LC-ESI-MS/MS. The identification of in vivo targets in blood cannot be accomplished without first studying the protein-binding behavior of platinum drugs in vitro; therefore, relevant studies are also summarized. This knowledge will further our understanding of the pharmacokinetics and toxicity of platinum anticancer drugs, and it will be beneficial for the rational design of metal-based anticancer drugs.
顺铂及其类似物在临床实践中被广泛用作化疗药物。静脉给药后，大量铂会与血液中的蛋白质结合。这种结合对于药物的运输、分布和代谢至关重要；然而，生物活性蛋白质与铂类药物之间的不可逆结合也可能导致毒性。因此，研究铂类药物在血液中的蛋白质结合行为非常重要。本综述总结了基于质谱的策略，用于鉴定和定量血液中与铂类抗癌药物结合的蛋白质，如离线高效液相色谱/电感耦合等离子体质谱（HPLC-ICP-MS）结合电喷雾电离质谱（ESI-MS/MS）以及多维液相色谱-电喷雾电离质谱（LC-ESI-MS/MS）。在不首先研究铂类药物体外蛋白质结合行为的情况下，无法完成血液中体内靶点的鉴定；因此，也总结了相关研究。这些知识将加深我们对铂类抗癌药物药代动力学和毒性的理解，并有助于金属基抗癌药物的合理设计。
